GTM-3, an Extra-Large Pore Enantioselective Chiral Zeolitic Catalyst.

The development of chiral zeolitic catalysts possessing extra-large pores and endowed with the capability of enantioselectively processing bulky products represents one of the greatest challenges in chemistry. Here, we report the discovery of GTM-3, an enantio-enriched extra-large pore chiral zeolite material with -ITV framework structure, obtained using a simple enantiopure organic cation derived from the chiral pool, N,N-ethyl-methyl-pseudoephedrinium, as the chiral-inductor agent. We demonstrate the enantio-enrichment of GTM-3 in one of the two enantiomorphic polymorphs using the two enantiomers of the organic cation. Interestingly, we prove the ability of this zeolitic material to perform enantioselective catalytic operations with very large substrates, here exemplified by the catalytic epoxide aperture of the bulky trans-stilbene oxide with alcohols, yielding unprecedented product enantiomeric excesses up to 30%. Our discovery opens the way for the use of accessible chiral zeolitic materials for the catalytic asymmetric synthesis of chiral pharmaceutical compounds.

Driving the Active Site Incorporation in Zeolitic Materials via the Organic Structure-Directing Agent Through Development of H-Bonds with Hydroxyl Groups.

(1S,2S)-N-methyl-pseudoephedrine (MPS) was used as organic structure-directing agent (OSDA) for the synthesis of Mg-doped nanoporous aluminophosphates. This molecule displays a particular conformational behavior, where the presence of H-bond donor and acceptor groups provide a rigid conformational space with one asymmetric conformation preferentially occurring. MPS drives the crystallization of Mg-containing AFI materials. Characterization of these materials shows that the OSDA incorporate as protonated species, arranged as head-to-tail monomers. Combination of three-dimensional electron diffraction with high-resolution synchrotron powder X-ray diffraction allowed to locate both the Mg and the organic species. Interestingly, results showed that the spatial incorporation of Mg is driven by the hydroxyl groups of the organic cation through the development of H-bonds with negatively-charged MgO4 tetrahedra. This work demonstrates that H-bond forming groups can be used to drive the spatial incorporation of low-valent dopants within zeolitic frameworks, a highly desired aim in order to control their catalytic activity and selectivity.

Self-assembly of chiral (1R,2S)-ephedrine and (1S,2S)-pseudoephedrine into low-dimensional aluminophosphate materials driven by their amphiphilic nature.

In an attempt to promote the crystallization of chiral inorganic frameworks, we explore the ability of chiral (1R,2S)-ephedrine and its diastereoisomer (1S,2S)-pseudoephedrine to act as organic building blocks for the crystallization of hybrid organo-inorganic aluminophosphate frameworks in the presence of fluoride. These molecules were selected because of their particular molecular asymmetric structure, which enables a rich supramolecular chemistry and a potential chiral recognition phenomenon during crystallization. Up to four new low-dimensional materials have been produced, wherein the organic molecules form an organic bilayer in-between the inorganic networks. We analyze by molecular simulations the trend of these chiral molecules to form these types of framework, which is directly related to their amphiphilic nature that triggers a strong self-assembly through hydrophobic interactions between aromatic rings and hydrophilic interactions with the fluoro-aluminophosphate inorganic units. Such a self-assembly process is strongly dependent on the concentration of the organic molecules.

Towards chiral distributions of dopants in microporous frameworks: helicoidal supramolecular arrangement of (1R,2S)-ephedrine and transfer of chirality.

A molecular-mechanics computational study is performed in order to analyze the arrangement of (1R,2S)-(-)-ephedrine molecules within the 12-MR channels of the AFI aluminophosphate microporous framework and the influence on the spatial distribution of dopants embedded in the tetrahedral network. Results showed that ephedrine molecules arrange exclusively as dimers by π-π stacking of the aromatic rings within the AFI channels. Interestingly, the asymmetric nature of ephedrine and the presence of H-bond-forming groups (NH2 and OH) involve a preferential orientation where consecutive dimers within the channels are rotated by an angle of +30°; this is driven by the establishment of inter-dimer H-bonds. This preferential orientation leads to the development of a supramolecular enantiomerically-pure helicoidal (chiral) arrangement of ephedrine dimers. In addition, the computational results demonstrate that the particular molecular structure of ephedrine imparts a strong trend to attract negative charges to the vicinity of the NH2(+) positively-charged groups. Hence divalent dopants such as Mg, whose replacement by trivalent Al in the aluminophosphate network involves the generation of a negative charge, will tend to locate close to the NH2(+) molecular groups, suggesting that an imprinting of the organic arrangement to the spatial distribution of dopants would be feasible. Combined with the trend of ephedrine to arrange in a helicoidal fashion, an enantiomerically-pure helicoidal distribution of dopants would be expected, thus inducing a new type of chirality in microporous materials.

A combination of proton spin diffusion NMR and molecular simulations to probe supramolecular assemblies of organic molecules in nanoporous materials.

In this work we show the use of high-resolution 1H MAS NMR to distinguish between two kinds of aggregation states of (1R,2S)-ephedrine, a chiral organic structure directing agent, occluded within AFI-type microporous aluminophosphates. We investigate in particular the supramolecular assembly of the molecules through π⋯π type interactions of their aromatic rings when confined within the one-dimensional AFI channels. A series of high-resolution two-dimensional spin diffusion spectra combined with molecular simulations and DFT calculations allowed us to distinguish different aggregation states of ephedrine molecules and precisely estimate the distances between the aromatic rings and their closest protons inside the zeolite channels as a consequence of distinct proton spin diffusion profiles.